Fibronectin and C4-binding protein are selectively bound by aggregated amyloid P component.
Serum amyloid P component (SAP) is a normal plasma protein, closely related to C-reactive protein, which is deposited together with amyloid fibrils in all forms of amyloidosis. It is also a normal constituent of human tissues, where it is found in vascular basement membranes and in association with the peripheral microfibrillar mantle of elastic fibres throughout the body. Very similar, highly conserved, homologous proteins are present in the sera of all vertebrates in which they have been sought, and in all cases these proteins display calcium-dependent binding affinity for agarose. The physiological function or pathogenetic significance of this reactivity are not known but we report here for the first time that under appropriate conditions human SAP can also bind certain serum glycoproteins. SAP, which had been aggregated either by direct conjugation to CNBr-activated Sepharose beads, or by complexing with anti-SAP antibodies immobilized on such beads, selectively took up fibronectin and C4-binding protein from whole normal human serum. The reaction was calcium dependent and the two ligands were bound independently of each other or of other serum constituents. Experiments with isolated fibronectin and SAP complexed by anti-SAP-Sepharose indicated that close association of pairs of SAP molecules was required for fibronectin to be bound and that each SAP dimer was capable of taking up a single molecule of fibronectin. There was no evidence that SAP in its native state in the serum was complexed with either fibronectin or C4-binding protein. The present findings significantly extend knowledge of the properties of SAP and open the way to characterisation of its physiological ligand(s) and thence to elucidation of its function.
D000682:Amyloid / Q000276:immunology; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D011232:Chemical Precipitation; D003181:Complement C4 / Q000276:immunology / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D012685:Sepharose / Q000276:immunology; D000683:Serum Amyloid P-Component
D000682:Amyloid; D002352:Carrier Proteins; D003181:Complement C4; D005353:Fibronectins; D007106:Immune Sera; D000683:Serum Amyloid P-Component; D012685:Sepharose; D004492:Edetic Acid; D002118:Calcium